Monitoring treatment using implantable telemetric sensors

ABSTRACT

Methods of and devices for monitoring the treatment of a human or non-human animal are disclosed. These involve a chip-sized passive sensor which is adapted (a) to receive and to rectify an electromagnetic signal with a frequency of 1-2 Ghz directed from outside the body towards it and to derive its operating power directly from the electromagnetic signal, and (b) to use its thus obtained operating power to transmit data relating to treatment by wireless telemetry to a receiver external to the body of the human or non-human animal. The data transmitted by the sensor is then processed to provide information on the treatment.

This invention relates to monitoring the treatment of human or non-humananimals by means of implantable passive telemetric sensors. It isapplicable to a variety of treatments but will be described hereinafterwith particular reference to hyperthermia treatment, it being understoodthat the invention in not restricted to this type of treatment. Also,the induction will be described in relation to human patients, althoughit is to be understood that the monitoring involved may also be appliedto non-human animals.

According to one aspect of the present invention, there is provided amethod of monitoring the treatment of a human or non-human animal, whichcomprises implanting into the body of the human or non-human animal ator close to the desired locus of treatment a passive sensor which isadapted (a) to receive and to rectify an electromagnetic signal with afrequency of 1-2 GHz directed from outside the body towards the sensorso as to derive its operating power from maid electromagnetic signal,and (b) to transmit date relating to treatment parameters by wirelesstelemetry to a receiver external to the body of the human or non-humananimal; and processing the data transmitted by said sensor to provideinformation on the treatment.

According to another aspect of the present invention, there is provideda device for implantation into the body of a human or non-human animal,which device comprises a passive sensor which is adapted (a) to receiveand to rectify an electromagnetic signal with a frequency of 1-2 GHzdirected from outside the body towards it and to derive its operatingpower from said electromagnetic signal, and (b) to transmit datarelating to treatment parameters by wireless telemetry to a receiverexternal to the body of the human or non-human animal.

According do to a third a third aspect of the present invention, thereis provided a system for monitoring the treatment of a human ornon-human animal, which system comprises (a) a first component implantedinto the body of the human or non-human animal at or close to the siteof treatment; and (b) a second component in the form of a unit externalto the body of the human or non-human animal,

characterized in that:

(A) said first component comprises an antenna, rectification circuitryand signal processing circuitry;

(B) said second comprises is a microwave source, a receiver, atransmit/receive antenna and control circuitry for controlling theoperation of the unit; and

(C) said first component is arranged:

(a) to receive and rectify an electromagnetic signal with a frequency of1-2 GHz transmitted by the antenna of said second component and toderive its operating power from said electromagnetic signal, and

(b) to transmit data relating to treatment parameters by wirelesstelemetry to said second component; and

(D) said second component is arranged to transmit an electromagneticsignal with a frequency of 1-2 GHz towards said first component and tointerrogate said first component to derive therefrom data pertaining tothe treatment which human or non-human animal is undergoing.

In one particular embodiment of the invention, the sensor is a miniaturepressure sensor; this may, for example, be associated with a stent whosefunction is to maintain the lumen patency of a duct, vessel or organ.Such devices may be employed at many sites within the body and mayprovide valuable information during the treatment of a wide range ofconditions. The sensor may, for example, be incorporated in atransjugular intrahepatic portosystemic shunt (TIPS) or in a stentwithin the renal artery.

The desired locus of treatment may be, for example, a tumour; a bloodvessel (for example, where levels of circulating species, or generalflow rates, are to be monitored); or a duct, e.g. the pancreatic duct orbile duct. Many other loci exist and will naturally be determinedaccording to the needs of the patient.

preferably, the sensor is associated with a therapeutic device which isalso implanted into the human or non-human animal body in the method ofthis invention. Non-limiting examples of the implanted therapeuticdevice include:

a device for delivering heat in a localised manner, e.g. to treat atumour;

pump for assisting blood flow;

a stent for ensuring lumen patency of hollow viscera and ducts, e.g.oesophagus, bile duct, pancreatic duct, colon, stomach, rectum andurethra;

a pressure sensor for detecting localised pressures, e.g. within a stentof the type just mentioned;

a flow meter for determining passage of a fluid through a duct;

a drug release device;

a pacemaker;

a detector for particular chemical or biological material or species,e.g. blood or tissue chemical content or cellular content;

or combinations of such devices.

Localised heating can be of benefit in several situations, for example:(a) to stop bleeding, e.g. of a tumour or in a non-malignant conditionsuch as benign ulcers of the stomach or duodenum. The therapeutic devicemay thus be an electrode or an assembly of electrodes which can beactivated (preferably remotely) so as to generate localised heating ofadjacent tissues. An electrode of this sort may, for example, bepositioned around a tumour of the prostate, colon, bladder, stomach orlung; it may likewise be positioned adjacent to a duodenal or stomachulcer.

The invention also finds application in surgical procedures involvingballoon dilatation and/or coronary stenting. These surgical procedurestend to encourage the formation of fibrous tissue which can lead tostenosis, e.g. blockage of a blood vessel after removal of thedilatation equipment. In accordance with this invention, such dangers ofstenosis may be removed or mitigated by heating the stent during acoronary stenting procedure or by applying heat adjacent to a regionundergoing balloon dilatation. Control of the heating process isassisted by sensing the temperature of the heated component.

The sensor associated with the therapeutic device will be configured torespond to a parameter (e.g. temperature, flow rate, pressure) which isof significance in the treatment regime being followed. Thus in thetreatment of a tumour by hyperthermia, the parameter sensed may betemperature; and in the treatment of an occluded duct, the parametersensed may be pressure.

The transmission of data from within the body to an external receivermay be accomplished using low power radiation in the radio frequency ormicrowave frequency bands. Such transmission is preferably intermittentrather than continuous and will generally be under the control ofmedical personnel or, in the case of a human patient of the patienthim/herself.

Advantageously, the sensor (and the therapeutic device also, if thisrequires electrical power to operate is/are empowered by wireless means.While in some instances batteries may be implanted as a power source,this is not preferred; the currently preferred mode of delivery is bymeans of an implanted antenna/rectifier device (a so-called “rectenna”)which receives electromagnetic radiation from an external source anddelivers electrical power derived therefrom. Typically, the power levelsinvolved for sensor applications are less than about 1 mW; at theselevels, the antenna portion of the rectenna can be implemented as afilamentary coil-shaped antenna for low frequencies or as a short dipoleantenna for high frequencies. A chip-sized (typically less than 1 mm³)rectifying circuit comprising a combination of rectifying diodes, astorage capacitor and (optionally) a filter circuit is mounted on theantenna. Typically, the sensor/rectenna combination occupies a volume ofaround 60 mm³ or less.

Electromagnetic radiation at a frequency of 1-2 GHz and with a powerdensity of 1 mW/cm² will provide such a rectenna with adequate operatingpower. This may advantageously be provided by an externaltransmit/receive unit which will direct electromagnetic radiationtowards the implanted rectenna in order to power up and interrogate thesensor electronics. Such a unit will operate in a duplex fashion,simultaneously transmitting the power signal to the implanted unit(s)and receiving the telemetry signal containing the data required from theunit(s).

To maximise the efficiency of the power delivery system, it may beadvantageous to use polarised electromagnetic radiation and acorrespondingly configured rectenna.

There exist many circumstances within the human or non-human body whereregular measurement of parameters of body function would provideinformation important for the management of a variety of disorders. Forexample, those tumours which generate marker substances could easily bemonitored by an implanted sensor in accordance with this invention.Monitoring of acute phase protein, and particularly of reactive c-phaseprotein, is commonly undertaken in many patients through the techniqueof venesection. Similarly, patients suffering from chemical imbalances(e.g. hormonal imbalance) could use an implanted sensor in accordancewith this invention to determine their hormonal status as and whenrequired. For example, in patients suffering from thyroid deficiency, athyroxin detector could be used to determine circulating levels ofthyroid. Certain cardiovascular and immunological problems have veryspecific blood-borne indicators of condition which may be monitored bymeans of the present invention. Such applications as mentioned abovefall within the scope of this invention. Equally, the sensor may be usedto monitor pharmacokinetics, e.g. when chronic administration of drugs(e.g. digoxin or tamoxifen) is required.

For a better understanding of the invention, and to show how the samemay be carried into effect, reference will now be made, by way ofexample, to the accompanying drawings, which illustrate an embodiment ofthe invention applied to a therapeutic system for hyperthermia treatmentof a liver tumour, and in which:

FIG. 1 illustrates schematically the basic sensor interrogation systemof this invention;

FIG. 2 shows more detail of the disposition of implanted components andtheir operation in hyperthermia treatment of a patient; and

FIGS. 3A and 3B illustrate stents implanted, respectively, in the colonand in the pancreatic duct.

Referring to FIG. 1, one or more sensor chips 1 are implanted into themalignant region of a patient's liver. Each sensor chip comprises threebasic elements, namely a rectenna 3, electronic processing circuitry 4in the form of an integrated circuit, and a sensing device 5. An antenna7 (see FIG. 2) is part of the rectenna 3. A sensor chip incorporatingthese components may be no more than 10 mm long, 2 mm wide and 1 mmthick. To activate the sensor chip, a reader/interrogator 6 is used toirradiate the sensor chip(s) with a radio signal which is of sufficientpower to enable the rectenna 3 to generate a voltage large enough tocause the electromagnetic component 4 of the sensor to function. Thereader unit 6 will normally be located just outside, and close to, thebody of the patient; it may for example be hand-held; attached to a beltaround the patient's body; or otherwise located in a substantially fixedposition relative to the body.

Referring to FIG. 2, a practical implementation of thereader/interrogation unit 6 of FIG. 1 is shown. A source 11 of radiowaves (typically in the frequency range 1000 MHz-2000 MHz) foods adirectional antenna 12 through a circulator 13. The transmit source 11may be modulated under control of an integrated circuit 14 whichprovides sign coding and processing capabilities. The unit furthercomprises a receiver 15 which receives signals transmittedtelemetrically by the implanted sensor and which supplies the receivedsignals to the integrated circuit 14 which is adapted to decipher codedtransmissions from the sensor chip 1. A display screen 16 is alsoprovided in the unit 6 for the purpose of displaying the informationreceived from within the patient.

By means of a system as just described, it may be possible to providerelatively simple, auto-regulated control of tumours which, because oftheir siting or their characteristics or the previous treatment historyof the patient are not susceptible to conventional methods of treatment.

The system as described may be used in conjunction with secondarytechniques, for example the direct injection of paracrine hormones or ofcells secreting paracrine hormones. These are believed to promoteapoptosis of tumours and/or to encourage infiltration of the heatedtumour by cells of the innate immune system.

In designing the components for implantation in the present invention,it is desirable to minimise the size of the components to reduce tissuedamage during the implantation step; to maximise their rigidity toincrease the accuracy with which they can be positioned within the bodyof a patient; and to encapsulate the components in non-toxic,non-reactive material. Further, the control system employed preferablyallows different modes of activation of the antenna elements 10-13 so asto permit variation of the spatio-temporal heat delivery.

FIGS. 3A and 3B show metallic or metal-containing stents S₁ and S₂,respectively, in the human colon and pancreatic duct. These serve tomaintain the lumen patency of the organs or ducts in which they areimplanted, and where partial or complete occlusion (e.g. by a tumour)has occurred. By implanting coupling elements and a rectenna inoperative connection with the stent, heat may be delivered to kill thetumour calls. As illustrated in FIG. 2, control and monitoring means maybe incorporated to provide telemetric control and operation of thehyperthermia treatment.

What is claimed is:
 1. A device for implantation into the body of ahuman or non-human animal, which device comprises a chip sized passivesensor which is adapted (a) to receive and to rectify an electromagneticsignal with a frequency of 1-2 GHz directed from outside the bodytowards said sensor, the sensor being adapted to derive its operatingpower directly from said electromagnetic signal, and (b) to use powerthus obtained by said sensor to transmit data relating to treatmentparameters by wireless telemetry to a receiver external to the body ofthe human or non-human animal in response to the receivedelectromagnetic signal with a frequency of 1-2 Ghz.
 2. A device asclaimed in claim 1, which is adapted to remain inactive and notconsuming any power unless said sensor is activated by an external radiosignal.
 3. A device as claimed in claim 1, wherein the device includesan antenna/rectifier to provide operating power from incomingelectromagnetic energy.
 4. A device as claimed in claim 3, wherein saidantenna/rectifier is adapted to provide operating power from incomingpolarized electromagnetic energy.
 5. A device as claimed in claim 1,wherein said sensor is a pressure sensor.
 6. A device as claimed inclaim 1, which further comprises a therapeutic device.
 7. A device asclaimed in claim 6 wherein said therapeutic device is one or more of:(1) a device for delivering heat in a localized manner, (2) a pump forassisting blood flow; (3) a stent for ensuring lumen patency of hollowviscera and ducts; (4) a pressure sensor for detecting localizedpressures; (5) a flow meter for determining passage of a fluid through aduct; (6) a drug release device; (7) a pacemaker; and (8) a detector forparticular chemical or biological material or species.
 8. A device asclaimed in claim 6, wherein said therapeutic device is a device fordelivering heat in a localized manner in order to treat a tumor.
 9. Amethod of monitoring treatment of a human or non-human animal, whichcomprises implanting into the body of the human or non-human animal ator close to a desired locus of treatment a chip size passive sensorwhich is adapted (a) to receive and to rectify an electromagnetic signalwith a frequency of 1-2 GHz directed from outside the body towards thesensor, with the said sensor deriving its operating power directly fromsaid electromagnetic signal, and (b) to use power thus obtained by saidsensor to transmit data relating to treatment parameters by wirelesstelemetry to a receiver external to the body of the human or non-humananimal in response to the received electromagnetic signal with afrequency of 1-2 Ghz; and processing the data transmitted by said sensorto provide information on the treatment.
 10. A system for monitoring thetreatment of a human or non-human animal, which system comprises (a) afirst component adapted to be implanted into the body of the human ornon-human animal at or close to a site of treatment; and (b) a secondcomponent in the form of a unit external to the body of the human ornon-human animal, wherein: (A) said first component is chip sized,comprises rectification circuitry and signal processing circuitry and isattached to an antenna; (B) said second component comprises a microwavesource, a receiver, a transmit/receive antenna and control circuitry forcontrolling wireless interrogation of said first component; and (C) saidfirst component is arranged: (a) to receive and rectify anelectromagnetic signal with a frequency of 1-2 GHz transmitted by theantenna of said second component, said first component being adapted toutilize the rectified signal strength to power active device within saidfirst component and (b) to transmit data relating to treatmentparameters by wireless telemetry to said second component in response tothe received electromagnetic signal with a frequency of 1-2 Ghz; and (D)said second component is adapted to transmit an electromagnetic signalwith a frequency of 1-2 GHz towards said first component and, usingoperating power derived from said electromagnetic signal when said firstcomponent is in use in the body of the human or non-human animal, tointerrogate said first component to derive therefrom data pertaining tothe treatment which the human or non-human animal is undergoing.
 11. Asystem as claimed in claim 8, wherein the antenna of the first componentis a filamentary coil shaped antenna.